What Is It, Health Benefits, Role in Cancer, and More

Author:Anna Hernández, MD

Editors:Alyssa Haag,Stefan Stoisavljevic, MD,Kelsey LaFayette, DNP, ARNP, FNP-C

Illustrator:Jessica Reynolds, MS

Copyeditor:Stacy Johnson, LMSW

What is autophagy?

Autophagy, meaning “self-eating,” is an intracellular degradation process that allows cells to recycle damaged intracellular components to generate energy and provide building blocks to create new cellular structures. 

In physiological conditions, autophagy acts as a housekeeping mechanism to ensure that damaged organelles and proteins are rapidly digested and cleared from the cell. They do not build up and prevent cells from functioning correctly. In response to metabolic stressors (e.g., nutrient deprivation, oxidative stress, or DNA damage), autophagic activity is upregulated to keep up with the increased metabolic demands, allow cells to work efficiently, and survive under stress conditions. For example, autophagy is essential in times of nutrient deprivation as it will enable cells to reutilize their cell components for energy and replace the depleted intracellular parts. In addition, autophagic activity contributes to the mobilization of cellular energy stores, like glucose, amino acids, and nucleic acids, which can then become available for energy production. 

In recent years, defects in autophagy-related genes have been associated with the development of several disorders, including cancer and neurodegenerative diseases like Alzheimer disease. Like many other physiologic processes, autophagy declines with age, likely contributing to damaged cells and protein accumulation. Various animal models and cellular studies indicate that increased autophagy activity may play a role in improved longevity and a longer lifespan. However, research on the topic still needs to be completed. 

Intracellular organelles.

What is the mechanism of autophagy?

Autophagy-related genes regulate autophagy. The process of autophagy starts when autophagy-related proteins are recruited sequentially to form a cup-shaped membrane called a phagophore. The phagophore then extends and surrounds damaged intracellular components by creating a double-membrane vesicle around them called an autophagosome. Once formed, the autophagosome undergoes a maturation process as it travels through the cytoplasm before fusing with a cell organelle called a lysosome. When the lysosome and the autophagosome fuse together, their contents merge, forming a structure known as the autophagolysosome. Inside the autophagolysosome, lysosomal enzymes start destroying the autophagosome contents (i.e., damaged intracellular components). The degradation products, which may include sugars, amino acids, nucleotides, and fatty acids, are released back into the cytoplasm for future cell use.

Although the formation of the autophagosome is the most critical and researched mechanism for autophagy, there are two other types of autophagy called microautophagy and chaperone-mediated autophagy. In microautophagy, the lysosome directly engulfs portions of the cytoplasm. In contrast, in chaperone-mediated autophagy, specific chaperone proteins bind to the intracellular cargo and transport it to the lysosome for degradation.

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How can autophagy be induced?

Autophagy is a cell-survival mechanism induced in response to several metabolic stressors, such as nutrient deprivation, organelle or DNA damage, hypoxia, and pathogen infection. 

Current research shows that starvation is a primary stimulus that can trigger autophagy. This is partly why fasting diets and calorie restriction have become popular ways to improve health and longevity in recent years. Fasting practices may positively affect certain conditions, including better seizure control for children with epilepsy, possibly due to neuroprotection. Common fasting practices include intermittent fasting, where individuals limit their calorie intake during certain hours of the day or certain days of the week, and prolonged fasting, where individuals may fast for several days at a time. During fasting, individuals may consume water, black coffee, tea, and other calorie-free beverages, but no solid foods or calorie-containing drinks are allowed. 

Although fasting can indeed have health benefits for some individuals, it does come with risks. For example, individuals who undergo fasting diets may experience low energy levels, leading to extreme tiredness, difficulty concentrating, and a low or depressed mood. In addition, skipping meals and severely limiting calories can be dangerous for certain people, including elderly individuals, children, and adolescents; people with a history of eating disorders; high-performance athletes; and individuals who are pregnant or breastfeeding. Additionally, fasting may not be safe for people with diabetes mellitus and individuals who take medications for high blood pressure or heart disease, who are more likely to develop electrolyte imbalances from fasting. 

What is the relationship between cancer cells and autophagy?

Autophagy appears to play a dual role in cancer development. In the early stages of cancer, autophagy suppresses tumor formation by degrading potentially harmful molecules that may contribute to cancer-cell formation; whereas in advanced stages, autophagy promotes tumor growth by allowing cancer cells to survive under stressful conditions. The induction of autophagy may also benefit cancer cells to escape from immune surveillance, resulting in resistance against anti-tumor immunotherapy. Due to the important role of autophagy in cancer development, many trials assess the effect of autophagy inhibitors and activators in cancer treatment. Although trials are showing promising results, further research is still required to turn autophagy modulation into a useful anti-tumor therapy.

What are the most important facts to know about autophagy?

Autophagy is an intracellular degradation process that allows cells to recycle damaged intracellular components to generate energy and provide building blocks to create new cellular structures. Additionally, autophagy increases when a cell faces metabolic stress like nutrient deprivation, oxidative stress, or DNA damage to improving cell survival. Autophagy involves encapsulating damaged proteins and organelles into a vesicle called the autophagosome, fusing with lysosomes so their contents can be digested. Defects in autophagy have been associated with several disorders, most notably cancer and neurodegenerative diseases. Although much has been discovered in the past few years about autophagy and its role in health and disease, further research is required to turn autophagy into a useful anti-aging and anti-tumor therapy. 

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Related links

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Resources for research and reference

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